In the last few decades, there has been a great development of longer sustained-release formulations including biodegradable or biocompatible synthetic polymers as drug delivery materials and bioactive substances, especially, peptides and salts thereof. Such formulations have a plurality of advantages in that they can significantly reduce inconvenience of patients caused by frequently administering the formulations to patients to improve patient compliance, maintain constant concentration of drugs in blood to reduce side effects, and cut down medical expenses.
Korean Patent Reg. No. 10-0442931 disclosed a method for preparation of sustained-release formulations in a microcapsule form, which dissolves polymeric carrier materials in any suitable organic solvent that does not dissolve pharmaceutical compounds, and adds aqueous medium containing excess of protective colloids and phase derivatives to the solution. But, this method requires complicated procedures in manufacturing the formulations and has very low production yield leading to a rise in price of a product.
Korean Patent Laid-Open No. 10-2005-0086708 disclosed a method for preparation of octreotide acetate micro particles of linear poly(lactide-co-glycolide) polymer that contains less than 1% of silicon oil or heptane.
Korean Patent Reg. 10-0194827 disclosed a method for preparation of microcapsules for zero-order releasing of bioactive polypeptides over more than 2 months, which prepares an aqueous oil emulsion that has an inner aqueous phase containing about 20 to 70% (w/w) of polypeptide and an oil phase containing copolymer or homopolymer with a molecular weight of 7,000 to 30,000 and compositional ratio of lactic acid/glycolic acid in the range of 80/10 to 100/0, and forms the emulsion into microcapsules.
Korean Patent Reg. No. 10-0409413 disclosed a method for preparation of microemulsion that comprises preparing the microemulsion by drying-in-water, and heat drying the emulsion at above glass transition temperature (Tg) of biodegradable polymer to considerably inhibit initial release of bioactive substances and to minimize amount of organic solvent used in the method. For this method, there is required above 50% of lactic acid among constitutional ingredients of the biodegradable polymer and Tg of at least 47° C. The method also has a drawback that bioactive substances may be modified by heat.
Korean Patent Reg. No. 10-0293882 disclosed novel salts, a method for preparation of the novel salts comprising cations derived from peptides containing basic groups and anions derived from polyester having carboxyl terminal, and use thereof for production of a sustained-release formulation type composition. However, the use comprises the steps of: freezing and forming drug and polymer into droplets; drying the droplets under vacuum conditions to form a transparent film; dispersing the film in dichloromethane and again drying the dispersion; compressing and molding the dried material; and administering the molded product by means of a syringe needle with relative larger diameter such as 16 or 18 gauge needle, which, therefore, has a problem of causing patients to experience a fear of pain.